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A transition-metal-free synthesis of pyridine derivatives by 6- endo - dig cyclization of N -propargyl enamines was developed. This method is environmentally friendly and is a high atom economy reaction that is easily accessed to provide pyridine derivatives in moderate to good yield by heating N -propargyl enamines in solvent without additives. The total synthesis of onychine was achieved in 51% yield in only two steps by using this method. [ABSTRACT FROM AUTHOR]

An efficient copper‐catalyzed cyclization of acetophenone and ammonium acetate with release of methane has been developed for the synthesis of polysubstituted pyridines. A series of 2,4,6‐triphenyl‐pyridines has been produced in good yields. This synthetic method is sustainable, simple, and environment‐friendly. [ABSTRACT FROM AUTHOR]

A facile approach to access polysubstituted pyridine derivatives starting from Baylis‐Hillman adducts is disclosed. The reactions proceeded smoothly by sequential AlCl3‐catalyzed condensation/aza‐Wittig/isomerization reactions, leading to the target products at room temperature within 24 h in moderate to good yields. Furthermore, the final products were evaluated in mycelial growth tests against Pythium dissimile, Botryotinia fuckeliana and Zymoseptoria tritici and showed potential activities. [ABSTRACT FROM AUTHOR]

• Two silver(I) complexes bearing mefenamic acid and pyridine derivatives were synthesized and characterized. • Antiproliferative activity towards MCF-7, HT-29, HepG2 and 3T3L1 cell lines was investigated. • The Ag(I) complexes exhibited considerably higher selectivity between the tested cancer and healthy cell lines than carboplatin. • Induction of apoptosis and ROS production were measured in MCF-7 cell line. Two Ag(I) complexes [Ag 2 (μ-mef) 2 (2-pymet) 2 ] 1 , [Ag 2 (μ-mef) 2 (2-pyet) 2 ] 2 containing mefenamic acid, 2-pyridinemethanol and 2-pyridineethanol were synthesized and characterized by using SCXRD, FT-IR, elemental and thermal analysis techniques. The complex 1 was synthesized as a single crystal whereas the complex 2 was obtained as a microcrystalline powder. The complex 1 consists of binuclear structure. The argentophilic interaction occurs among silver(I) ions due to the short Ag⋯Ag distance (2.8710(10) Å). Two Ag(I) centers are connected by carboxylato oxygen-bridge to form the binuclear metal core. The FT-IR spectra and thermal analysis studies confirmed that both complexes exhibited similar structures. In vitro antiproliferative activity of both complexes were evaluated against MCF-7, HT-29 and HepG2 cancer cell lines. The apoptotic effects and intracellular ROS generation from both complexes were investigated in MCF-7 cell line by flow cytometry analysis. The XTT and LDH assays revealed that both complexes showed strong antiproliferative activity with higher selectivity towards cancer cells compared to the normal cells. In addition, Annexin V/propidium iodide assay exhibited that apoptotic cell number was increased in MCF-7 cells with increasing concentrations of Ag(I) complexes. Furthermore, both complexes induced the ROS generation considerably in MCF-7 cells suggesting the possible pro-oxidant activity of the novel synthesized Ag(I) complexes. Taken together, these findings provide a notable support for potential utility of Ag(I) complexes as novel anticancer agents against numerous kind of carcinogenesis. [ABSTRACT FROM AUTHOR]

With the aim of discovering a lead compound for pyridine‐based fungicide bearing adamantane moiety, a series of novel O‐alkyl/benzyl‐1‐(adamantan‐1‐yl)‐2‐(pyridin‐3‐yl)ethan‐1‐one oximes were synthesized from 3‐methylpyridine, ethyl (adamantan‐1‐yl)carboxylate, and alkoxyamine or benzoxyamine hydrochloride. The in vitro antifungal activity against four pathogenic fungi was evaluated, and some compounds exhibited good antifungal activity. Compounds 3d and 3f demonstrated strong activity against Sclerotinia sclerotiorum, with EC50 values of 11.25 and 12.87 μg/mL, respectively; 3b, 3c, and 3k had notable activity against Botrytis cinerea, with EC50 values of 12.78, 12.57, and 11.97 μg/mL, respectively. For Rhizoctonia Solani, 3d and 3g showed sufficient activity with EC50 values of 9.66 and 8.90 μg/mL, respectively. In addition, 3d and 3g demonstrated moderate activity against Colletotrichum orbiculare, with EC50 values of 14.32 and 15.83 μg/mL, respectively. A series of novel O‐alkyl/benzyl‐1‐(adamantan‐1‐yl)‐2‐(pyridin‐3‐yl)ethan‐1‐one oximes were synthesized, and their in vitro antifungal activities against four pathogenic fungi were evaluated. Compounds 3d and 3f possessed strong activity against Sclerotinia sclerotiorum; and 3b, 3c, and 3k had notable activity against Botrytis cinerea. For Rhizoctonia Solani, 3d and 3g showed sufficient activity. [ABSTRACT FROM AUTHOR]

Abstract Solid-state acidochromic (SSAC) molecules often exhibit dual-coloured rather than multi-coloured stimuli-responsive properties. To obtain the molecule possessing a multi-coloured emission switching based on one specific solid-state of a single molecule, a new D-π-A type 1,4-dihydropyridine derivative 4a containing barbituric acid and N , N -dimethylaniline unit, which contains multiple sites that can be combined with H+, is designed and synthesized. Compound 4a is confirmed to have twisted molecular conformation by crystallographic data and exhibits aggregation-induced emission characteristic. Upon the stimuli of acid-base system, 4a exhibits rare seven-coloured emission switching in solid-state. Another 1,4-dihydropyridine derivative 4b based on 1,3-dimethylbarbituric acid is synthesized for comparison. Compared with 4b which only displays three-coloured solid-state emission switching, 4a exhibits a more abundant colour change, which might be attributed that the nitrogen atoms on the N H bonds are also involved in the process of protonation and deprotonation, slowing down the transformation between D-π-A and A-π-A structures. The results provide a new idea for the development of multicolour SSAC materials. Graphical abstract Image 1 Highlights • Synthesis and characterization of two new 1,4-dihydropyridine derivatives. • These AIE-active compounds exhibit solid-state acidochromism. • Barbituric acid-based compound shows rare seven-coloured emission switching in solid-state. [ABSTRACT FROM AUTHOR]

The novel 1,4-bis(2,6-dibromo-4-formylphenoxy)butane (3), prepared from 3,5-dibromobenzaldehyde (1), reacted with different hydrazines 4a–4d and active methylene containing compounds 9a–9d to give the corresponding bis(hydrazones) 5a–5d and bis(cinnamonitriles) 11a–11d, respectively. Both bis(2-cyanoacetic acid hydrazide) derivative 5d and bis(thioacrylamide) derivative 11a were taken as synthetic precursors for the synthesis of the target molecules bis(pyridine-2(1H)-thione) derivative 10 and 13a–13c and their bis(2-methylsulfanylpyridine) derivative 14 and 17a–17c. Another synthetic route was designed to prepare the target molecules 14 and 17a–17c in a better yield using pyridine-2(1H)-thione) derivative 15 and 19a–19c. Characterization of the newly prepared compounds via elemental analyses and spectral data are established. [ABSTRACT FROM AUTHOR]

Methods for synthesizing new condensed pyrano[4, 3-b]pyridine derivatives from 2-methyl-2-ethyltetrahydropyran-4-one were developed. The neurotropic activities of the compounds were studied. [ABSTRACT FROM AUTHOR]

Graphical abstract A procedure for preparing a 4′-triphenylborate-substituted derivative of the 2,2′:6′,2″-terpyridine ligand is described. Such a modification renders the terpyridine ligand anionic, which enables unique design possibilities for coordination chemistries involving metal ions relative to the unsubstituted parent ligand. Abstract A procedure for preparing a 4′-triphenylborate-substituted derivative of the 2,2′:6′,2″-terpyridine ligand is described. Such a modification renders the terpyridine ligand anionic, which enables unique design possibilities for coordination chemistries involving metal ions relative to the unsubstituted parent ligand. Proof-in-principle that this new ligand can coordinate to transition metals was provided through the synthesis of a novel nickel complex. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • This method allows the mild route for functionalized bispyrazolo[3,4- b :4′,3′- e ]pyridines. • The reaction temperature decreased from 220–250 °C to 130 °C compared to conventional methods. • A large proportion of the products precipitated directly from the mixture at room temperature. Abstract A mild and efficient method for the synthesis of bispyrazolo[3,4- b :4′,3′- e ]pyridines from 5-aminopyrazoles and aromatic aldehydes using an inexpensive FeCl 3 catalyst is reported. The reaction temperature was reduced from 220–250 °C to 130 °C compared to conventional methods. A large proportion of the products precipitated directly from the mixture at room temperature. Aliphatic and α,β-unsaturated aldehydes selectively resulted in formation of the corresponding 1 H -pyrazolo[3,4- b ]pyridine derivatives. A possible domino reaction mechanism was also proposed. Several aryl alkynyl groups were introduced to these tricyclic molecules via the Sonogashira coupling reaction. [ABSTRACT FROM AUTHOR]

Methyl 2-(bromomethyl)thiophene-3-carboxylates reacted with substituted 2-hydroxybenzonitriles to give methyl 2-[(2-cyanophenoxy)methyl]thiophene-3-carboxylates which underwent tandem cyclization to benzo[4,5]furo[3,2-b]thieno[2,3-d]pyridin-4(5H)-ones. [ABSTRACT FROM AUTHOR]

The condensation of malononitrile with hydrogen sulfide and aldehydes in the presence of triethylamine in ethanol at room temperature afforded 4-alkyl(aryl, hetaryl)-2,6-diamino-3,5-dicyano-4H-thiopyrans. Treatment of the latter in situ with alkali in DMF, followed by addition of an alkylating agent, led to the formation of 4-alkyl(aryl, hetaryl)-2-alkoxycarbonyl(aroyl, carbamoyl)-3,6-diamino-5-cyanothieno[2,3-b]- pyridines. [ABSTRACT FROM AUTHOR]

A systematic study of the synthesis and properties of 1‐aza‐, 4‐aza‐, and 1,4‐diaza[4]helicenes as well as the previously unknown S‐shaped double 1,4‐diaza[4]helicenes has been reported. The synthetic route to the aza‐ and diaza[4]helicenes involved an electrophile‐induced cyclization of 3(2)‐alkynyl‐2(3)‐(naphthalen‐1‐yl)azines (i.e., quinoxaline, pyrazine, pyridine), which were prepared in two steps from the commercially available ortho‐dihalo‐substituted azine. Trifluoroacetic acid (TFA) and ICl were used as electrophiles. The ICl‐promoted cyclization provided the 5‐iodo derivatives of the aza‐ and diaza[4]helicenes in yields of 47–71 %. The use of TFA as the electrophile afforded the helicenes along with isomeric products from an alternative cyclization and subsequent 1,2‐shift of the C–C bond (e.g., naphtho[2,1‐f]quinoxalines or naphtho[2,1‐a]phenazines, 87–89 % total yield, 1.5–1.8:1 ratio). The presence of an iodine substituent in the hetero[4]helicenes allowed for the introduction of an alkynyl group by using a Sonogashira reaction. The subsequent cycloizomerization upon treatment with TFA gave the S‐shaped double 1,4‐diaza[4]helicenes. The molecular structures and crystal packing of the synthesized hetero[4]helicenes relative to those of [4]carbohelicene have been discussed. [ABSTRACT FROM AUTHOR]

A simple and general method for the synthesis of new imidazopyridines bearing an aminopyridinyl, chromenyl, or quinolinyl moiety in the C2 position was developed. The Knoevenagel reaction between imidazo[1,2-a]pyridine-2-carbaldehyde 1 and malononitrile resulted in the formation of starting material 2. Subsequently, intramolecular cyclization between the cyano group of 2 and acetophenones, naphtols, hydroxyquinolines, or phenols, gave 3, 4, 5, and 6 compounds, respectively. This is a simple, reproducible, and environmentally friendly method of synthesizing substituted imidazopyridines using water as a solvent or under solvent-free conditions. [ABSTRACT FROM AUTHOR]

Reactions between hydroxyl substituted 4′-phenyl-terpyridine ligands p -hydroxyl-4′-phenyl-terpyridine ( L 1 ), m -hydroxyl-4′-phenyl-Terpyridine ( L 2 ) and o -hydroxyl-4′-phenyl-terpyridine ( L 3 ) and ZnCl 2 led to the formation of the complexes [Zn(Cl) 2 L 1 ] ( 1 ), [Zn(Cl) 2 L 2 ] ( 2 ) and [Zn(Cl) 2 L 3 ] ( 3 ), respectively, which were characterized by IR, 1 H NMR, 13 C NMR, elemental analysis and single crystal X-ray diffraction, along with their photoluminescent properties. The bindings of the compounds with bovine hemoglobin (BHb) were measured by spectroscopic and molecular docking methods Fluorescence study at the room temperature indicated that the fluorescent intensity of BHb was reduced upon the addition of the compounds by the static quenching mechanism. Based on the results of molecular docking, it could be suggested that the binding process of the compounds with BHb is a spontaneous molecular interaction, in which van der Waals’ forces and hydrogen bonds play major roles. The binding constants for the interactions of the compounds with BHb and the numbers of binding sites were also determined. [ABSTRACT FROM AUTHOR]

The IR and Raman spectra of pyridine perchlorate salt (PyHClO 4 ) have been recorded in the 4000–300 and 3200–200 cm − 1 regions, respectively. The structure and vibrational spectra of pyridine salt have been investigated by means of ab initio and density functional theory (DFT) calculations. To examine the efficiency of basis sets in predicting the vibrational spectra of ClO 4 − 1 ion, several basis sets were used with the B3LYP and B2PLYP levels of theory. It was shown that the 6-311(3df) basis set gives reasonably vibrational wavenumbers for simulation of perchlorate ion experimental vibrational wavenumbers. Therefore, the B3LYP/6-311G(3df) level was used to calculate the vibrational spectra of pyridine perchlorate salt in CH 3 CN solution. For comparison, the vibrational wavenumbers were also calculated at the B3LYP/aug-cc-pVTZ level. The geometry of PyHClO 4 was calculated in the gas phase as well as in solutions, using SCRF-PCM method. According to these calculations, the structure and hydrogen bonding in PyHClO 4 is highly affected by media. Two hydrogen bonding systems between ClO 4 − 1 and pyridinium ions were recognized. The nature of these hydrogen bonds is theoretically investigated by using atoms in molecule (AIM) method and natural bond orbital (NBO) analysis. A normal coordinate analysis was performed by using the internal coordinates calculated at the B3LYP/6-311G(3df,p) level for the vibrational normal modes of the titled compound. [ABSTRACT FROM AUTHOR]

Two series of aromatic hydrazone derivatives bearing 1 H -pyrrolo[2,3- b ]pyridine moiety ( 7a – r , 8a – i , 12a – b , 13a – c , 16a – d and 17a – e ) were designed, synthesized and evaluated for the IC 50 values against four cancer cell lines (A549, HepG2, MCF-7and PC-3). Two selected compounds ( 7c and 17e ) were further evaluated for the activity against c-Met, Flt-3, VEGFR-2 and EGFR kinases. The data indicated that targets compounds were selective for c-Met kinase. And the most promising compound 7c was further studied in terms of dose-dependent, time-dependent and cell apoptosis. Most of the compounds showed excellent cytotoxicity activity, especially the most promising compound 7c with the IC 50 values of 0.82 ± 0.08 μM, 1.00 ± 0.11 μM, 0.93 ± 0.28 μM and 0.92 ± 0.17 μM against A549, HepG2, MCF-7 and PC-3 cell lines and 0.506 μM against c-Met kinase. Structure–activity relationships (SARs) and docking studies indicated that the activities of the phenyl hydrazone derivatives ( 7a – r and 8a – i ) were superior to that of the heterocyclic hydrazone series ( 12a – b , 13a – c , 16a – d and 17a – e ). What's more, the further studies indicated that the target compounds can induce apoptosis of A549 cells and arrest efficiently the cell cycle progression in G2/M phase of A549 cells. [ABSTRACT FROM AUTHOR]

With the aim of discovering potential and selective inhibitors targeting ROS1 kinase, we rationally designed, synthesized and evaluated two series of novel 2-amino-pyridine derivatives with 1-phenylethoxy at C-3 and C-4 position. The enzymic assays results indicated that six of the new compounds 13b - 13d and 14a - 14c showed remarkably higher inhibitory activities against ROS1 kinase. The most promising compounds, 13d and 14c displayed the most desired ROS1 inhibitory activity with IC 50 values of 440 nM and 370 nM respectively. Furthermore, 13d and 14c displayed ROS1 inhibitory selectivity of about 7-fold and 12-fold, relative to that of ALK sharing about 49% amino acid sequence homology in the kinase domains. They also showed good anti-proliferative effects against ROS1-addicted HCC78 cell lines with the IC 50 values of 8.1 μM and 65.3 μM, respectively. Moreover, molecular docking and molecular dynamics simulation studies disclosed that compound 14c and 13d shared similar binding poses with Crizotinib except the selective binding site of ROS1. It also gave a probable molecular explanation for their activity and selectivity, which the methoxyl group in benzene ring was the crucial to the selectivity to ROS1 versus ALK. [ABSTRACT FROM AUTHOR]

A series of pyrrolo[2,3- b ]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety were synthesized, and evaluated for their antiproliferative activity against four cancer cell lines (HT-29, A549, H460, and U87MG) and six tyrosine kinases (c-Met, Flt-3, PDGFR-β, VEGFR-2, EGFR, and c-Kit) inhibitory activities in vitro . Most compounds showed moderate to excellent potency, with the most promising analogue 32 showing Flt-3/c-Met IC 50 value of 1.16/1.92 nM. Structure-activity relationship studies indicated that the hydrogen atom served as R 1 group was benefited to the potency, and mono-electron-withdrawing groups (mono-EWGs) on the phenyl ring (such as R 3 = 4-F) showed a higher preference for antiproliferative activity. [ABSTRACT FROM AUTHOR]

A simple method for the synthesis of highly functionalized 2‐amino‐6‐(methylthio)pyridine‐3,5‐dicarbonitriles is presented. In this method, pyridine derivatives are synthesized from the reaction of malononitrile, aromatic aldehydes, nitroketene dithioacetal in the presence of ethylene diamine. The notable features of this method are the simple Experimental procedure, short reaction time, and good yields. [ABSTRACT FROM AUTHOR]

The title compound 6-phenyl-4-(p-tolyl)pyridin-2(1H)-one was synthesized via one-pot, three component reaction of (E)-1-phenyl-3-(p-tolyl)-2-propen-1-one, ethyl 2-nitroacetate and ammonium acetate in refluxing ethanol, as a shiny green crystalline solid in 83% yield. Its structure was characterized by spectral studies and unambiguously corroborated by X-ray diffraction crystallography. The crystals of title compound are monoclinic, sp. gr. P21/n, a = 11.8346(7) Å, b = 13.4413(9) Å, c = 17.7626(10) Å, ß = 99.479(5)°, and Z = 8. All the rings in molecule of the title compound are planar. Hydrogen interactions play significant role in stabilizing the crystal structure and the supramolecular aggregate of molecules is facilitated by strong N-H···O and C-H···O type of hydrogen interactions. [ABSTRACT FROM AUTHOR]

A novel compounds of 4,6-diaryl-2-oxo(imino)-1,2-dihydro-pyridine-3-carbonitriles has been synthesized by reaction of 1-(3-chlorophenyl)-3-(pyren-1-yl)-1 H-pyrazole-4-carbaldehyde with different 1-(substituted phenyl)ethanones and ethyl cyanoacetate or malononitrile in presence of ammonium acetate. Structure of the newly synthesized compounds was elucidated from chemical and spectroscopic data. [ABSTRACT FROM AUTHOR]

A group of new 2-alkyloxypyridine-3-carbonitriles linked pyrenyl-pyrazole functions has been obtained via reaction of 1-(3-chlorophenyl)-3-(pyren-1-yl)-1 H-pyrazole-4-carbaldehyde with different methyl aryl ketones. The newly compounds were assured by spectroscopic and elemental analysis. [ABSTRACT FROM AUTHOR]

Self-assembly of 1:1:2 MII(BF4)2 (M=Zn or Fe), pyrazine-2,5-dicarbaldehyde ( 1) and 2-(2-aminoethyl)pyridine gave trimetallic triangle architectures rather than the anticipated tetrametallic [2×2] squares. Options for the nontrivial synthesis of 1 are considered, and synthetic details provided for both preferred routes. Rare cyclohelicate triangle architectures are observed for the pair of structurally characterized yellow-brown [Zn3 L3](BF4)6 and dark green [Fe3 L3](BF4)6 complexes of the neutral bis-terdentate Schiff base L. In order to form these pyrazine-edged triangles, the octahedral metal ions-with all 6 N-donors provided by the terdentate binding pockets of two L-are located 0.4-0.5 Å out of the plane of the bridging pyrazines, towards the center of the triangle. Density functional theory calculations confirm that simple particle counting entropic arguments, which predict triangles over squares, are correct here, with the triangles shown to be energetically favored over the corresponding squares. However, importantly, DFT analysis of these and related triangle versus square systems also show that vibrational contributions to entropy dominate and may significantly influence the preferred architecture, such that simple particle counting cannot in general be reliably employed to predict the observed architecture. [ABSTRACT FROM AUTHOR]

Polyfunctionalized 1,2,3,4-tetrahydropyridines were synthesized in up to 90% yield by condensation of ethyl acetoacetate with cyclic aminals in methanol. [ABSTRACT FROM AUTHOR]

Synthesis of new thiopyran fused spirooxindoles (spiro[indoline-3,4′-thiopyran]-2-ones) were achieved by a multicomponent reaction ofN-methyl isatin, malononitrile/ethyl cyanoacetate, andβ-oxodithioester usingN,N′-dimethylaminopyridine as the catalyst. [ABSTRACT FROM AUTHOR]

A simple and convenient procedure for the preparation of some unknown 2,3-disubstituted 5-iodo-1 H-pyrrolo[2,3- b]pyridines from readily available starting materials by Fischer indole cyclization in polyphosphoric acid is described. The present methodology provides an alternative synthetic approach to the synthesis of 5-iodo-7-azaindole scaffold. All synthesized compounds were characterized by IR, MS, 1H and 13C NMR, and elemental analysis. [ABSTRACT FROM AUTHOR]

A synthesis of bis(dihydropyridine-3,5-dicarbonitrile) by a three-component reaction of one equivalent of bis-cyanoacetamides with two equivalents of both arylaldehydes and malononitrile in ethanol-containing piperidine is reported. Bis-cyanopyridones could also be obtained by the condensation of bis-cyanoacetamides with substituted arylidenemalononitriles in the presence of piperidine, chitosan, or montmorillonite as basic catalysts. The cytotoxicity of the synthesized products against the heterogeneous human epithelial colorectal adenocarcinoma cell line (Caco-2) was assessed by WST-1 assay with concentration dependent cellular growth inhibitory effect especially for compounds 5l, 5h, and 5d. The dose response curves indicate that IC50 were 87 ± 3.11 μg/mL, 104 ± 4.78 μg/mL, and 108 ± 5.12 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

A series of some substituted diethyl 4-(2-chloroquinolin-3-yl)-2,6-dimethylpyridine-3,5-dicarboxylates has been synthesized from substituted diethyl4-(2-chloroquinolin-3-yl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates (1,4-DHPs) by treating the latter with SiO2-HNO3 which proved to be a better oxidant in terms of product yield, reaction time, and cost. Further, these compounds were screened for their antimicrobial activity. All the diethyl 4-(2-chloroquinolin-3-yl)-2,6-dimethylpyridine-3,5-dicarboxylates exhibited more potent activities than the corresponding 1,4-DHPs. Further, docking simulation of the most active and least active compounds 3e and 2e into Escherichia coli topoisomerase II DNA Gyrase B was also performed. [ABSTRACT FROM AUTHOR]

An efficient one-pot, catalyst-free, and four-components procedure for the synthesis of novel 10b-hydroxy-4-nitro-5-phenyl-2,3,5,5a-tetrahydro-1 H -imidazo[1,2-a]indeno[2,1-e]pyridin-6(10b H )-one derivatives from corresponding diamine, nitro ketene dithioacetal, aldehydes and 1,3-indandione in ethanol has been achieved upon a Knoevenagel condensation-Michael addition-tautomerism-cyclisation sequence. All the newly synthesized compounds were screened for molecular docking studies. Molecular docking studies were carried out using the crystal structure of HIV protease enzyme. Some of the compounds obtain minimum binding energy and good affinity toward the active pocket of HIV protease enzyme in compare with Saquinavir as a standard HIV protease inhibitor. [ABSTRACT FROM AUTHOR]

Cerium(IV) carboxymethylcellulose (CMC −Ce) was found to be a highly efficient, eco-friendly and recyclable heterogeneous catalyst for the synthesis of 2,4,6-triarylpyridine derivatives in excellent yields via one-pot multicomponent reaction of various benzaldehydes, acetophenones, and ammonium acetate under solvent-free condition. Moreover, the present protocol has the merits of easy work-up, short reaction times, and high yields. [ABSTRACT FROM AUTHOR]

A novel tandem one-pot method for the synthesis of polysubstituted pyridine derivatives has been developed via Knoevenagel-type reaction and subsequent 6 π electrocyclization of the Blaise reaction intermediates and 3-formylchromones. Short reaction time, moderate to good yields and excellent functional group tolerance have been accomplished in this protocol. [ABSTRACT FROM AUTHOR]

A novel series of pyridine-based derivatives was synthesized and evaluated for their inhibitory activity against dipeptidyl peptidase-4 (DPP4). 5-Aminomethyl-6-(2,4-dichlorophenyl)-4-[(1 H-1,2,4-triazol-1-yl)methyl]pyridine-2-carboxylic acid was identified as a potent (IC 0.57 nM) and selective DPP4 inhibitor (DPP8/DPP4 = 238). A docking study of this compound revealed a hydrogen-bonding interaction with the Arg125 residue of the enzyme providing a potential target residue for further structural optimization. [ABSTRACT FROM AUTHOR]

A convergent and regioselective synthesis of silicon-bridged 4-arylpyridines has been developed through a rhodium-catalyzed [2+2+2] cycloaddition of silicon-containing diynes with nitriles. The absorption and emission properties of these compounds have been examined and could be tuned by varying the substituent on the benzene ring, as well as through the protonation or alkylation of the nitrogen atom on the pyridine ring. A catalytic asymmetric synthesis of silicon-centered axially chiral spirocyclic derivatives has also been achieved with high enantioselectivity by using a newly modified MeO-MOP (MeO-MOP=2-(diphenylphosphino)-2′-methoxy-1,1′-binaphthyl) derivative as the chiral ligand. These spirocyclic compounds were found to be CPL-active (CPL=circularly polarized luminescence), representing the first CPL-active compounds based on the chirality at silicon. [ABSTRACT FROM AUTHOR]

Three new cadmium(II)-metal(II) cyanide complexes, [Cd(4aepy) 2 (H 2 O) 2 ][Ni(CN) 4 ] ( 1 ), [Cd(4aepy) 2 (H 2 O) 2 ][Pd(CN) 4 ] ( 2 ) and [Cd(4aepy) 2 (H 2 O) 2 ][Pt(CN) 4 ] ( 3 ) [4aepy = 4-(2-aminoethyl)pyridine], have been synthesized and characterized by elemental, thermal, FT-IR and Raman spectral analyses. The crystal structures of 1 and 2 have been determined by single crystal X-ray diffraction technique, in which they crystallize in the monoclinic system and C 2/ c space group. The M(II) [M(II) = Ni(II), Pd(II) and Pt(II)] ions are coordinated with the carbon atoms of the four cyanide groups in the square planar geometries and the [M(CN) 4 ] 2− ions act as counter ions. The Cd(II) ions display an N 4 O 2 coordination sphere with a distorted octahedral geometry, the nitrogen donors belonging to four molecules of the organic 4aepy that act as unidentate ligands and two oxygen atoms from aqua ligands. 3D supramolecular structures of 1 and 2 were occurred by M⋯π and hydrogen bonding (N H⋯N and O H⋯N) interactions. Vibrational assignments of all the observed bands were given and the spectral properties were also supported the crystal structures of the complexes. A possible decompositions of the complexes were investigated in the temperature range 30–800 °C in the static atmosphere. [ABSTRACT FROM AUTHOR]

The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a-2i, 4a-4i. In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine (1) directly or via N-[5-bromo-2-methylpyridine-3-yl]acetamide (3) with several arylboronic acids produced these novel pyridine derivatives in moderate to good yield. Density functional theory (DFT) studies were carried out for the pyridine derivatives 2a-2i and 4a-4i by using B3LYP/6-31G(d,p) basis with the help of GAUSSIAN 09 suite programme. The frontier molecular orbitals analysis, reactivity indices, molecular electrostatic potential and dipole measurements with the help of DFT methods, described the possible reaction pathways and potential candidates as chiral dopants for liquid crystals. The anti-thrombolytic, biofilm inhibition and haemolytic activities of pyridine derivatives were also investigated. In particular, the compound 4b exhibited the highest percentage lysis value (41.32%) against clot formation in human blood among all newly synthesized compounds. In addition, the compound 4f was found to be the most potent against Escherichia coli with an inhibition value of 91.95%. The rest of the pyridine derivatives displayed moderate biological activities. [ABSTRACT FROM AUTHOR]

Cyclometallation of 8-methylquinoline and 2-(dimethylamino)-pyridine in an iridium-based pincer complex is described. The C−H activation of 2-(dimethylamino)pyridine is not chelation assisted, which has not been described before for Csp3−H bonds in cyclometallation reactions. The mechanism of the cyclometallation of 2-(dimethylamino)pyridine was studied by DFT calculations and kinetic measurements. [ABSTRACT FROM AUTHOR]

We have developed a novel method for synthesis of various kinds of nitroarenes by using a three-component ring transformation (TCRT) of dinitropyridone with ketones in the presence of ammonium acetate as nitrogen source. This method requires only simple manipulations and mild reaction conditions. Furthermore, the modification of obtained nitropyridine or nitroaniline frameworks can be easily obtained only changing a commercially available substrates. [ABSTRACT FROM AUTHOR]

A method for the synthesis of pyridine derivatives based on a triple cascade reaction catalyzed by chiral secondary amines was developed. The resulting cyclohexenes (three C-C bonds were formed) were obtained in good yields with good diastereoselectivities and excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

The unusual square-planar (SP) structure of four-coordinate AlIII-complexes with the phenyl-substituted tridentate bis(imino)pyridine (PhI2P) ligand has been studied by a combination of density functional theory (DFT) calculations, frontier molecule orbital (FMO), nucleus-independent chemical shift (NICS) and strain/interaction analyses. The calculations disclose that: (i) the aromaticity shifting from the pyridine ring to the alumina-imidazolate metallacycle, and (ii) the small strain energy imposed on the ligand backbone are two favourable factors for driving the overall SP coordination of the AlIII ion. Meanwhile, the calculations reveal that the SP coordination of the AlIII ion is also influenced by the fourth ligand that is bonded to the AlIII ion. The less steric demanding ligand could ensure the stronger aromaticity of the alumina-imidazolate metallacycle and small strain energy on the ligand backbone. Additionally, the calculations predict that GaIII and InIII ions favour the SP geometry in the analogue PhI2P-ligated complexes, while BIII and TlIII ions are reluctant to adopt the SP coordination with the PhI2P ligand. Overall, all of these findings would be helpful for the synthesis of more unknown low-valent main-group metal complexes bearing the bis(imino)pyridine ligand. [ABSTRACT FROM AUTHOR]

4-[4-(dimethylamino)phenylazo]pyridine (further denoted as G) representing a type of push-pull molecules can be intercalated into α- and γ-modifications of zirconium phosphate (α-ZrP and γ-ZrP) and into zirconium (4-sulfophenyl)phosphonate (ZrSPP). The obtained intercalates form single phases with interlayer distances of 12.75, 16.31, and 24.11 Å for α- ZrP·0.2G·1.5H2O, γ-ZrP·0.2G·1.5H2O, and ZrSPP·0.5G·1H2O, respectively. The increase of the interlayer distance upon intercalation suggests that the molecules of the intercalated guest lie parallel to the host layers. All intercalates were further characterized by IR and UV/Vis spectroscopy. The arrangement of the guests in the interlayer space was determined by molecular simulation methods. The calculations were performed sepa- rately for protonated and unprotonated forms of the guest in the models of hydrated and dehydrated α-ZrP and γ-ZrP intercalates. In the case of the α-ZrP intercalate, the presence of interlayer water stabilizes the head-to-tail arrangement of the guest molecules. Dehydration of this intercalate disturbs their arrangement, mainly in the case of protonated guest molecules. In the case of dehydrated γ-ZrP, the guest molecules are headto- tail ordered, and the guest molecules in the hydrated form of γ-ZrP are more disordered than in the dehydrated intercalate. The simulations also describe a layer shift present in the dehydrated γ-ZrP intercalate, which explains why the rehydration of this intercalate is not possible. [ABSTRACT FROM AUTHOR]

Cu-catalyzed tandem cyclization of 2-(2-iodophenyl)imidazo[1,2- a ]pyridines with selenium for the practical synthesis of the benzo[ b ]selenophene-fused imidazo[1,2- a ]pyridines occurred smoothly via Ullmann-type Se -arylation and C sp2 –H selenation. A variety of benzo[ b ]selenophene-fused imidazo[1,2- a ]pyridines were easily obtained in moderate-to-high yields. Single-crystal X-ray analysis of 2a revealed that the benzo[ b ]selenophene and imidazopyridine rings are almost coplanar. The maximum absorption of tetracyclic compound 2a was red-shifted by 45–47 nm from those of imidazo[1,2- a ]pyridine and benzo[ b ]selenophene. [ABSTRACT FROM AUTHOR]

A facile, one-pot method for the synthesis of 2-ferrocenylpyridines is described. When reacted with propargylamine, α,β-alkynic ketones produced N -propargylic β-enaminones in situ, which, in the presence of copper(I) chloride, underwent electrophilic cyclization to afford 2-ferrocenylpyridine derivatives in good to high yields. This cyclization was found to be general for a variety of α,β-alkynic ketones and tolerated the presence of aryl groups with electron-withdrawing and electron-donating substituents. The enrichment of the pyridine core with a ferrocenyl moiety, in addition to benzoyl groups, may offer potential for the synthesis of molecules of pharmacological interest. [ABSTRACT FROM AUTHOR]

A facile synthetic route to an important intermediate 4-amino-2,6-dichloropyridine was developed. Oxidation of 2,6-dichloropyridine as a starting material gave pyridine N-oxide derivative which was subjected to nitration followed by reduction. Subsequent nitration of the product and nucleophilic displacement reaction were carried out to afford fully substituted energetic pyridine derivatives. Most of the synthetic reactions proceeded under mild conditions. [ABSTRACT FROM AUTHOR]

Starting with 4-piperidone, new 5,6,7,8-tetrahydroimidazo[2′,1′:2,3]thiazolo [5,4- c]pyridines were synthesized. Structures of these compounds were confirmed by 1H NMR, 13C NMR, MS and elemental analysis. [ABSTRACT FROM AUTHOR]

Current researches have showed that N3, N5-diaryl-2, 6-dimethyl -1, 4-dihydropyrine-3, 5-dicarboxamide analogues demonstrate notable anti-tubercular activity. In this study, Hantzsch condensation was used to design and synthesize new analogues of dihydropyridine (DHP). Different diary carboxamides were inserted at positions 3 and 5 of the DHP ring. 4(5)-chloro-2-ethyl-5(4)-imidazolyl moiety was considered at position 4 of the DHP ring. The structures of prepared ligands were characterized using TLC followed by FT-IR, elemental analysis, Mass and proton NMR. Results of anti-tubercular activity have indicated all the prepared ligands 3a-f inhibit the mycobacterium tuberculosis growth and the most potent compounds were 3c (3,4-Cl) and 3b (4-Cl). The in-vitro obtained data are agreement with our computational predictions in terms of partial atomic charge of carbonyl moieties at the positions 3 and 5 of dihydropyridine ring and the logP of the molecules. [ABSTRACT FROM AUTHOR]

The present study reports a microwave-assisted method for the synthesis of twelve novel tricyclic 1,4-dihydropyridine derivatives in which dimethyl-substituted cyclohexane and / or tetrahydrothiophene rings are fused to the DHP ring. The structures of the compounds were confirmed by spectral methods and elemental analysis. The potassium channel opening effects of the compounds were determined on rat mesenteric arteries and urinary bladders. The obtained results indicated that some compounds produced mesenteric artery-selective relaxant properties and the effects of these compounds were mediated through ATP-sensitive potassium channels. The replacement of the second tetrahydrothiophene ring with dimethyl-substituted cyclohexane ring led to more active compounds. Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. The unsubstituted nitrogen atom on the 1,4-dihydropyridine ring and one of the sulfonyl oxygens were found to be important for the formation of hydrogen bonds to stabilize the compound in the center of the cavity. The nature and position of phenyl ring substituents were also effective on the activity of the compounds. Finally, a theoretical study was established to predict the ADME of the most active compounds. [ABSTRACT FROM AUTHOR]

Several dihydropyrimidinones/thiones, 1,4-dihydropyridines, and pyridine derivatives were prepared in very good yields and purity values. The corresponding reactions were carried out by employing a bulk Preyssler heteropolyacid H14[NaP5W29MoO110] as an efficient and recyclable catalyst. The preparation of pyridine derivatives was carried out not through a usual procedure, i.e., the opening of the γ-pyrone ring of 3-formylchromone. In general, reactions took place in solvent-free conditions at 80°C during short reaction times. [ABSTRACT FROM AUTHOR]

A DMAP catalyzed synthesis of new 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines was studied, in a view to react 4-chloroquinazolines with poorly nucleophilic alcohols such as benzylic alcohols, via a simple and cheap S N Ar reaction approach. A fast (1 h) general operating procedure, affording good reaction yields, was achieved under microwave irradiation. Thus, a series of 35 molecules was obtained and evaluated in vitro on the K1 multi-resistant Plasmodium falciparum strain, in parallel with a cytotoxicity assessment on the human HepG2 cell line. 5 hit-molecules were identified, presenting both promising antiplasmodial activity (1.5 μM < IC 50 < 2 μM) and low cytotoxicities (25 μM < CC 50 < 45 μM). Apart for 2 molecules, the global series displayed a satisfying solubility in the aqueous biological media. Structure-activity relationships showed that the molecules presenting a benzyloxy moiety were less cytotoxic than the ones bearing a phenoxy moiety at position 4 of the quinazoline ring. It also appeared that the introduction of a heteroaryl moiety afforded inactive compounds. Finally, the most active and selective molecules (Selectivity Index = 22–27) were the ones presenting either an unsubstituted benzyloxy group or a phenoxy group, this last bearing a p -bromo or an o -acetyl substituent. [ABSTRACT FROM AUTHOR]

A series of [1,2,4]triazolo[4,3- a ]pyrazine derivatives ( 4a – 4i ) were designed, synthesized and evaluated for their c-Met kinase inhibition and antitumor activity against SNU5 gastric cell line in vitro. Among these compounds, 4d was found to show the highest activity against c-Met and high selectivity against the tumor cells which are believed to be dependent on the c-Met oncogene amplification, because 4d selectively inhibited c-Met while had no effect on other 59 kinases. In vivo efficacy study on human gastric (MKN-45) and human non-small cell lung (NCI-H1993) tumor xenograft in nude mouse demonstrated that 4d · CH 3 SO 3 H had a better inhibiting activity than SGX-523 in a dose-dependent manner. When tested in mice, compound 4d · CH 3 SO 3 H was found to have biological half-lives and plasma exposure values higher than those of JNJ-38877605, and its long-term toxicity and acute toxicity turned out to be acceptable, all of which indicates that 4d · CH 3 SO 3 H is a desirable drug candidate. [ABSTRACT FROM AUTHOR]